Poverty and InequalitySexual and Reproductive HealthFamily, Maternal & Child HealthMethodology

Penile Immune Activation and Risk of HIV Shedding: A Prospective Cohort Study

TitlePenile Immune Activation and Risk of HIV Shedding: A Prospective Cohort Study
Publication TypeJournal Article
Year of Publication2017
AuthorsPatel, EU, Kirkpatrick, AR, Grabowski, MK, Kigozi, G, Gray, RH, Prodger, JL, Redd, AD, Nalugoda, F, Serwadda, D, Wawer, MJ, Quinn, TC, Tobian, AA
JournalClin Infect Dis
Date PublishedMar 15
ISBN Number1058-4838
Accession Number28011606
Keywordsgenital inflammation, human immunodeficiency virus (HIV), immune activation, male circumcision, sexual transmission.

Background: Genital immune activation is suspected to modulate local human immunodeficiency virus (HIV) RNA levels and the risk of sexual HIV transmission. Methods: A prospective, observational cohort study of 221 HIV-infected men undergoing male circumcision (MC) was conducted in Rakai, Uganda. Penile lavage samples collected from the coronal sulcus at baseline and 4 weekly visits after MC were assayed for pro-inflammatory cytokines and HIV RNA. The main analysis was limited to 175 men with detectable HIV plasma viral load (VL > 400 copies/mL; n = 808 visits). The primary exposures of interest were individual and total cytokine detection at the previous postoperative visit. Adjusted prevalence risk ratios (adjPRR) of detectable HIV shedding (VL > 40 copies/mL) were estimated by Poisson regression models with generalized estimating equations and robust variance estimators and included adjustment for plasma HIV VL. Findings: Among men with a detectable plasma VL, penile HIV shedding was detected at 136 visits (16.8%). Detectable interleukin (IL)-1beta (adjPRR = 2.14; 95% confidence interval (CI) = 1.02-4.48), IL-6 (adjPRR = 2.24; 95% CI = 1.28-3.90), IL-8 (adjPRR = 2.42; 95% CI = 1.15-5.08), IL-10 (adjPRR = 2.51; 95% CI = 1.67-3.80), and IL-13 (adjPRR = 1.87; 95% CI = 1.15-3.03) were associated with penile HIV shedding at the subsequent visit. Men with 2-4 (adjPRR = 2.36; 95% CI = 1.08-5.14) and 5-7 (adjPRR = 3.00; 95% CI = 1.28-7.01) detectable cytokines had a greater likelihood of detectable penile HIV shedding at the subsequent visit, compared to men with